Development of the novel therapeutic strategy for diabetic nephropathy through anti-inflammatory effects.

我们已经证明，低度炎症，微炎症，参与糖尿病肾病以及动脉粥样硬化的发病机制。我们最近报道，抗炎药，如他汀类药物和噻唑烷二酮显示肾脏保护作用，通过抗炎作用在糖尿病动物。在本研究中，1）我们诱导糖尿病骨桥蛋白基因敲除（KO）小鼠。骨桥蛋白基因敲除小鼠显示肾脏组织损伤和炎症反应的改善。2)我们发现GLP-1受体在单核细胞/巨噬细胞和肾小球内皮细胞上表达。GLP-1受体激动剂通过抗炎作用对糖尿病大鼠肾脏有保护作用。提示骨桥蛋白在糖尿病肾病的发病中起一定作用，GLP-1受体激动剂可能对糖尿病肾病的治疗有益。

We have demonstrated that low grade inflammation, microinflammation, is involved in the pathogenesis of diabetic nephropathy as well as of atherosclerosis. We have recently reported that anti-inflammatory agents such as statin and thiazolidinedione show renoprotective effects through anti-inflammatory actions in diabetic animals. In this study, 1) We induced diabetes into osteopontin knockout(KO) mice. Osteopontin KO mice showed the improvement of tissue injuries and inflammatory reactions in the kidney. 2) We found that GLP-1 receptor is expressed on monocte/macrophage and glomerular endothelial cells. GLP-1 receptor agonist showed renoprotective effects on diabetic rats through anti-inflammatory actions. These results suggest that osteopontin play a role in the pathogenesis of diabetic nephropathy and GLP-1 receptor agonist might be beneficial for the treatment of diabetic nephropathy.